The regulation of the family of UDP glucuronosyltransferase enzymes is being studied by means of DNA, RNA and protein chemistry. The transferase system inducible by phenobarbital-like and polycyclic hydrocarbon-like compounds is essential for detoxification via glucuronidation of many lipophilic foreign and endogenous compounds. Antibodies raised against a purified mouse transferase (Mr about 51,000) were used to immuno-enrich transferase mRNA from mouse and rat liver. Recombinant cDNA clones (three from rat and one from mouse) were developed in the plasmid pBR322 from transferase mRNA and are undergoing characterization. Messenger RNA complementary to the rat cDNA clone pUDPGTR-2 (2000 bp) is inducible by phenobarbital and specifies a 52,000-dalton protein. Messenger RNAs complementary to the other two rat transferase clones (pUDPGTR-1 and pUDPGTR-3) are constitutive, and each encodes a 52,000-dalton polypeptide. Each of the rat cDNA clones recognizes a 2300-nt mRNA, although each clone is distinct by restricton enzyme analysis. The two contitutive clones share extensive homology; pUDPGTR-2 has less homology to these other two clones. The mouse transferase cDNA clone (1850 bp) recognizes two constitutive mRNAs (1900 and 2200 nt) which generate 51,000-dalton proteins. In the rat a 52,000-dalton transferase, translated from total RNA, undergoes processing by dog pancreatic microsomes, resulting in peptide cleavage of a 2000-dalton fragment and with no evidence of glycosylation. In the mouse a 50,000-dalton transferase translated from total mRNA undergoes processing in the presence of dog pancreatic microsomes to the mature form of 51,000 daltons by peptide cleavage and glycosylation. Further characterization of the types of transferase forms specified by these clones is underway. A human transferase form with a high pI, already purified to more than 90% homogeneity, is undergoing further steps of chromatography to obtain a more highly purified preparation for characterization and antibody production to enable us to isolate and characterize human transferase cDNA clones.